Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex
Copyright © 2020 The Authors, Ribonucleotide reductases (RNRs) are a diverse family of enzymes that are alone capable of generating 2′-deoxynucleotides de novo and are thus critical in DNA biosynthesis and repair. The nucleotide reduction reaction in all RNRs requires the generation of a transient a...
| Hlavní autoři: | , , , |
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| Médium: | Článek |
| Jazyk: | English |
| Vydáno: |
American Association for the Advancement of Science (AAAS)
2021
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| On-line přístup: | https://hdl.handle.net/1721.1/136072 |
| _version_ | 1826217064938864640 |
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| author | Kang, Gyunghoon Taguchi, Alexander T Stubbe, JoAnne Drennan, Catherine L |
| author_facet | Kang, Gyunghoon Taguchi, Alexander T Stubbe, JoAnne Drennan, Catherine L |
| author_sort | Kang, Gyunghoon |
| collection | MIT |
| description | Copyright © 2020 The Authors, Ribonucleotide reductases (RNRs) are a diverse family of enzymes that are alone capable of generating 2′-deoxynucleotides de novo and are thus critical in DNA biosynthesis and repair. The nucleotide reduction reaction in all RNRs requires the generation of a transient active site thiyl radical, and in class I RNRs, this process involves a long-range radical transfer between two subunits, a and b. Because of the transient subunit association, an atomic resolution structure of an active a2b2 RNR complex has been elusive. We used a doubly substituted b2, E52Q/(2,3,5)-trifluorotyrosine122-b2, to trap wild-type a2 in a long-lived a2b2 complex. We report the structure of this complex by means of cryo–electron microscopy to 3.6-angstrom resolution, allowing for structural visualization of a 32-angstrom-long radical transfer pathway that affords RNR activity. |
| first_indexed | 2024-09-23T16:57:32Z |
| format | Article |
| id | mit-1721.1/136072 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:57:32Z |
| publishDate | 2021 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1360722021-10-28T03:04:35Z Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex Kang, Gyunghoon Taguchi, Alexander T Stubbe, JoAnne Drennan, Catherine L Copyright © 2020 The Authors, Ribonucleotide reductases (RNRs) are a diverse family of enzymes that are alone capable of generating 2′-deoxynucleotides de novo and are thus critical in DNA biosynthesis and repair. The nucleotide reduction reaction in all RNRs requires the generation of a transient active site thiyl radical, and in class I RNRs, this process involves a long-range radical transfer between two subunits, a and b. Because of the transient subunit association, an atomic resolution structure of an active a2b2 RNR complex has been elusive. We used a doubly substituted b2, E52Q/(2,3,5)-trifluorotyrosine122-b2, to trap wild-type a2 in a long-lived a2b2 complex. We report the structure of this complex by means of cryo–electron microscopy to 3.6-angstrom resolution, allowing for structural visualization of a 32-angstrom-long radical transfer pathway that affords RNR activity. 2021-10-27T20:30:40Z 2021-10-27T20:30:40Z 2020 2021-07-15T18:23:45Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136072 en 10.1126/SCIENCE.ABA6794 Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Kang, Gyunghoon Taguchi, Alexander T Stubbe, JoAnne Drennan, Catherine L Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex |
| title | Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex |
| title_full | Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex |
| title_fullStr | Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex |
| title_full_unstemmed | Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex |
| title_short | Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex |
| title_sort | structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex |
| url | https://hdl.handle.net/1721.1/136072 |
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